OBJECTIVE To examine the effects of an antisense oligodeoxynucleotide for human NPY mRNA on in vivo LHRH release. The present study examines the effects of an antisense oligodeoxynucleotide (AS) for human neuropeptide Y (NPY) mRNA on pulsatile LHRH release in vivo using the push-pull perfusion method in female ovariectomized monkeys. After 6 h of control perfusion, 10 5M of the AS NPY was infused for 8 h, which was followed by an additional 4 h of control perfusion. As a control for AS, an oligodeoxynucleotide containing the same bases in a scrambled sequence (SC) was similarly examined. LHRH and NPY levels in perfusate samples, collected in 10-min fractions, were measured by RIA. AS NPY infusion resulted in a significant decrease in mean NPY release starting 2 h after the initiation of infusion, and continuing until shortly after the end of AS infusion (p<0.05, n=7). AS NPY also suppressed mean LHRH release significantly (p<0.05, n=7) The AS NPY-induced LHRH suppression started 2 h after the initiation of AS infusion, and continued throughout AS infusion, lasting for the entire period of the exp eriment. In contrast, SC NPY did neither result in significant changes in NPY release nor LHRH release. These data suggest that NPY release in the stalk-median eminence plays an important role in the control of pulsatile release of LHRH in vivo in the rhesus monkey. FUTURE DIRECTIONS We will examine the role of NPY Y1 receptors. KEY WORDS pulsatile NPY release, pulsatile LHRH release, antisense NPY mRNA. FUNDING NIH HD15433 & RR00167 PUBLICATIONS Kasuya, E., Mizuno, M., Watanabe, G., and Terasawa, E. Effects of an antisense oligodeoxynucleotide for neuropeptide-Y mRNA on in vivo LHRH release in ovariectomized female rhesus monkeys. Regul. Peptide 75-76 319-325, 1998. [J]